1. Field of the Invention
Collagen is the principal structural protein present in vertebrates. It has many properties which make it particularly desirable for the fabrication of medically useful devices. Natural collagen is readily available from a variety of domestic animals. The major portion of its structure varies little between mammalian species; and the positions of the distinguishing and structually significant amino acid residues (glycine, proline, and hydroxyproline), are uniquely consistent in the main helical portion of the atelopeptide collagen. This fundamental similarity is associated with characteristically low levels of immunogenic activity. Many immunogenic determinants are in the non-helical protein appendages extending from the terminal portions of the native molecule. These non-helical extensions, telopeptides, represent less than five percent of the naturally occurring molecule and can be removed through limited proteolysis. The treatment produces a disaggregation of discrete undenatured collagen molecules from the fibrous matrix (i.e. solubilization) and a substantial reduction in the ability of such molecules to elicit an immunologic response in a host different from the collagen source.
While the telopeptides are important sites of immunogenicity and their presence in collagen is undesirable in medical applications, the telopeptides play an important structural role in naturally occurring collagen. The telopeptides are the primary sites of both intra- and intermolecular cross-links. It is this portion of the molecule which provides the structural integrity of native collagen fibers. Moreover, there is evidence that the telopeptides direct the process of fibrogenesis through promoting the orderly accretion of constituent molecules into large structurally signifcant fibers. Thus, the removal of the telopeptides also removes that portion of the molecule which in the natural state appears essential to the formation and subsequent stability of native collagen fibers.